A number of human disorders are characterized by degeneration or loss of specific cells, resulting in pathology associated with reduction or absence of cell function. Such diseases include neurodegenerative diseases and diabetes.
The incidence of neurodegenerative diseases, including Alzheimer's, Parkinson's and motor neuron diseases, have tripled in the last 20 years (Pritchard C, et al., Public Health, 2004 118:268-283). Given the aging population, it has been estimated that there will be more than 100 million people worldwide affected with Alzheimer's disease alone by 2050 (Scorer C A., Drug Discov. Today, 2001 6:1207-1219). These central nervous diseases are irreversible and characterized by the progressive loss of neurons.
Similarly, diabetes affects an increasing number of people. Currently over 18 million Americans suffer from this disease. Approximately 5 to 10% of the diabetes patients are Type 1 diabetics affecting mostly children and young adults. Type 1 diabetes is an autoimmune disease that irreversibly destroys the insulin-producing beta-cells that constitute up to 80% of the pancreatic islets.
Current treatments for diseases characterized by cell loss and/or reduction in normal cell function include exogenous administration of cell products, such as insulin in the case of diabetes. However, such treatment is expensive and fraught with complications. Further, no effective treatment exists for patients suffering from neurodegenerative diseases because neuronal regeneration in the central nervous system is limited and/or compromised in these patients.
Embryonic stem cells are a possible tool for replacement of diseased or lost cells. In addition, stem cells potentially provide valuable research and drug screening tools. However, there are currently significant limitations associated with these cells. In particular, the cells have tremendous plasticity, possessing multiple independent differentiation pathways (Filip S, et al., J Cell Mol Med., 2004 8:572-7). As a consequence, some of these cells undergo spontaneous and premature differentiation in culture, resulting in heterogeneous populations of cells, that is, populations containing some undifferentiated cells and some differentiated cells. Further, differentiated cells themselves may be heterogeneous in such a culture, having mixed lineage.
Use of a heterogeneous population of stem cells as starting material in a process directed to producing differentiated cells is disadvantageous since only a limited number of a desired type of differentiated cell can be produced from such a starting material.
However, obtaining desired cell types in sufficient quantities is not the only obstacle to efforts to develop stem cell replacement therapeutics and research tools. For example, prior to potential transplants, strict screening of the transplant material for contamination of undifferentiated or partially differentiated cells is currently required to prevent formation of stem cell-derived tumors (teratomas). Further, use of differentiated stem cells as drug screening tools may be of limited use where mixed populations of cells are present, since less than optimal signal to noise ratios may be obtained.
Another limitation of current methods of working with embryonic stem cells is the necessity of culturing the cells in the presence of a feeder layer of cells. In particular, human embryonic stem cells are often cultured with a feeder layer including mouse cells. This can result in uptake of mouse proteins or other molecules by the stem cells, with negative implications for use of the stem cells in medical procedures, research or drug screening.
Thus, methods, compositions and systems for producing and maintaining a substantially homogeneous population of undifferentiated embryonic stem cells, and particularly human embryonic stem cells, are needed.
In addition to a continuing need for methods, compositions and systems for producing and maintaining a substantially homogeneous population of undifferentiated embryonic stem cells, methods, compositions and systems for producing and maintaining a substantially homogeneous population of a desired differentiated cell type, particularly human differentiated cells, are necessary.